Lipid structure-dependent CD1d functional stabilization and immunomodulation of endogenous glucosylceramides

Synthetic methods for monoglycosyl ceramides with various fatty acyl groups were developed, enabling the synthesis of representative brain glycolipids. The immunomodulatory activities of these lipids, depending on their fatty acyl structures, were then examined via CD1d and Mincle. Potent binding of CD1d to endogenous GlcCer with a longer unsaturated fatty acid, such as C24:1, was observed. This binding partially inhibited the interaction with other anti-gens, and it would stabilize the role of CD1d in presenting lipid antigens to NKT cells.